Recent published reports on the isolation and successful culturing of the first human pluripotent stem cell lines have generated great excitement and have brought biomedical research to the edge of a new frontier (National Institutes of Health, Office of the Director, “Stem Cells: A Primer”). Stem cells have the ability to divide for indefinite periods in culture and to give rise to specialized cells. They are best described in the context of normal human development. Human development begins when a sperm fertilizes an egg and creates a single cell that has the potential to form an entire organism. This fertilized egg is totipotent, meaning that its potential is total. In the first hours after fertilization, this cell divides into identical totipotent cells. This means that either one of these cells, if placed into a woman's uterus, has the potential to develop into a fetus. In fact, identical twins develop when two totipotent cells separate and develop into two individual, genetically identical human beings. Approximately four days after fertilization and after several cycles of cell division, these totipotent cells begin to specialize, forming a hollow sphere of cells, called a blastocyst. The blastocyst has an outer layer of cells and inside the hollow sphere, there is a cluster of cells called the inner cell mass.
The outer layer of cells will go on to form the placenta and other supporting tissues needed for fetal development in the uterus. The inner cell mass cells will go on to form virtually all of the tissues of the human body. Although the inner cell mass cells can form virtually every type of cell found in the human body, they cannot form an organism because they are unable to give rise to the placenta and supporting tissues necessary for development in the human uterus. These inner cell mass cells are pluripotent—they can give rise to many types of cells but not all types of cells necessary for fetal development. Because their potential is not total, they are not totipotent and they are not embryos. In fact, if an inner cell mass cell were placed into a woman's uterus, it would not develop into a fetus.
The pluripotent stem cells undergo further specialization into stem cells that are committed to give rise to cells that have a particular function. Examples of this include blood stem cells, which give rise to red blood cells, white blood cells and platelets; and skin stem cells that give rise to the various types of skin cells. These more specialized stem cells are called multipotent.
While stem cells are extraordinarily important in early human development, multipotent stem cells are also found in children and adults. For example, consider one of the best understood stem cells, the blood stem cell. Blood stem cells reside in the bone marrow of every child and adult, and in fact, they can be found in very small numbers circulating in the blood stream. Blood stem cells perform the critical role of continually replenishing our supply of blood cells—red blood cells, white blood cells, and platelets—throughout life. A person cannot survive without blood stem cells.
Multipotent stem cells have not been found for all types of adult tissue, but discoveries in this area of research are increasing. For example, until recently, it was thought that stem cells were not present in the adult nervous system, but, in recent years, neural stem cells have been isolated from the rat and mouse nervous systems. The experience in humans is more limited. In humans, neural stem cells have been isolated from fetal tissue and a kind of cell that may be a neural stem cell has been isolated from adult brain tissue that was surgically removed for the treatment of epilepsy. In animals, it has been shown that some adult stem cells previously thought to be committed to the development of one line of specialized cells are able to develop into other types of specialized cells. For example, recent experiments in mice suggest that when neural stem cells were placed into the bone marrow, they appeared to produce a variety of blood cell types. In addition, studies with rats have indicated that stem cells found in the bone marrow were able to produce liver cells. These exciting findings suggest that even after a stem cell has begun to specialize, the stem cell may, under certain conditions, be more flexible than first thought.
Research on human adult stem cells suggests that these multipotent cells have great potential for use in both research and in the development of cell therapies. For example, there would be many advantages to using adult stem cells for transplantation. If one can isolate the adult stem cells from a patient, coax them to divide and direct their specialization and then transplant them back into the patient, it is unlikely that such cells would be rejected by the patient's immune system. The use of adult stem cells for such cell therapies could reduce the practice of using stem cells that were derived from human embryos or human fetal tissue, sources that trouble many people on ethical grounds.
Stem cells can be made to differentiate under certain culture conditions. However, in some applications it is desirable to maintain stem cells in a non-differentiated state. Additional methods for assaying the differentiation status of stem cells are needed.